1.Adra2a Regulates LPS-Induced Inflammation in Hepatocytes of Lbp-/- Mice via the MAPK Signaling Pathway
Sai LIU ; Bin FU ; Sidi LI ; Zhida CHEN ; Yue ZHANG ; Zhongkun GUO ; Yongan WANG ; Kezhou WANG
Laboratory Animal and Comparative Medicine 2026;46(2):212-221
ObjectiveTo investigate the mechanism by which adrenoceptor alpha 2A (Adra2a) regulates lipopolysaccharide (LPS)-induced inflammation in primary hepatocytes from lipopolysaccharide-binding protein (LBP) knockout mice (Lbp-/-). MethodsPrimary hepatocytes from C57BL/6J and Lbp-/- mice were isolated using a two-step perfusion method. An in vitro inflammatory model was established by LPS stimulation, and an in vivo inflammatory mouse model was established by intraperitoneal injection of LPS. The in vitro experiments were grouped as follows: Control group, LPS group, BRL+LPS group, OE-NC+LPS group, and OE-Adra2a+LPS group. The Control group served as the blank control. The LPS group involved stimulating primary hepatocytes with LPS. The BRL+LPS group involved pretreating primary hepatocytes with BRL-44408 maleate followed by LPS stimulation. The OE-NC+LPS group involved transfecting primary hepatocytes with an empty vector followed by LPS stimulation. The OE-Adra2a+LPS group involved transfecting primary hepatocytes with a lentivirus overexpressing Adra2a, followed by LPS stimulation. The in vivo experimental groups were divided into Control', LPS', BRL+LPS', OE-NC+LPS', and OE-Adra2a+LPS' groups. The Control' group served as the blank control. The LPS' group received intraperitoneal injection of LPS. The BRL+LPS' group received intraperitoneal injection of BRL-44408 maleate for pretreatment, followed by LPS injection. The OE-NC+LPS' group received intraperitoneal injection of empty vector for pretreatment, followed by LPS injection. The OE-Adra2a+LPS' group received intraperitoneal injection of a lentivirus overexpressing Adra2a for pretreatment, followed by LPS injection. Cell viability after Adra2a inhibition and overexpression was assessed via the Cell Counting Kit-8 (CCK-8) assay. RT-qPCR measured changes in gene expression levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) after Adra2a inhibition and overexpression. Western blotting was performed to detect Adra2a protein expression and phosphorylation levels of extracellular signal-regulated kinase 1/2 (ERK1/2), p38 mitogen-activated protein kinase, and c-Jun N-terminal kinase (JNK) following LPS stimulation. ResultsIn vitro experiments revealed that LPS stimulation significantly decreased Adra2a protein expression in primary hepatocytes from C57BL/6J mice compared to the Control group (P<0.05), whereas it increased in primary hepatocytes from Lbp-/- mice (P<0.001). Compared to the LPS group, the BRL+LPS group exhibited significantly increased cell viability (P<0.01), reduced TNF-α, IL-6, and IL-1β gene transcription levels (P<0.01, P<0.001, P<0.001), and decreased phosphorylation levels of MAPK signaling pathway-related proteins ERK1/2, p38, and JNK (P<0.01, P<0.001, P<0.001). Compared with the OE-NC+LPS group, the OE-Adra2a+LPS group showed significantly decreased cell viability (P<0.001), increased gene transcription levels of TNF-α, IL-6, and IL-1β genes (P<0.001, P<0.01, P<0.001), and elevated phosphorylation levels of MAPK signaling pathway-related proteins ERK1/2, p38, and JNK (P<0.001, P<0.01, P<0.001). In vivo experiments showed that, compared with the LPS' group, the BRL+LPS' group exhibited significantly reduced phosphorylation levels of MAPK signaling pathway-related proteins ERK1/2, p38, and JNK (P<0.001, P<0.01, P<0.01). In the OE-Adra2a+LPS' group, the phosphorylation levels of ERK1/2, p38, and JNK were significantly elevated compared to the OE-NC+LPS' group (P<0.01, P<0.001, P<0.01). ConclusionLPS stimulation can cause a significant increase in Adra2a protein expression in primary hepatocytes of Lbp-/- mice. Adra2a protein can regulate the level of LPS-induced inflammation in primary hepatocytes of Lbp-/- mice through the MAPK signaling pathway.
2.Mechanism of IGF2BP2 regulation of PPAR-γ/GLUT4 pathway in insulin resistance induced by sodium arsenite exposure in HepG2 cells
Shiqing XU ; Zhida HU ; Qiyao ZHANG ; Siqi ZHAO ; Yujie WANG ; Xiaohui WANG ; Teng MA ; Li WANG
Journal of Environmental and Occupational Medicine 2025;42(4):400-407
Background Arsenic is an environmentally harmful substance that causes hepatic insulin resistance and liver damage, increasing the risk of type 2 diabetes mellitus. Objective To explore whether the insulin-like growth factor 2 mRNA binding protein 2 (IGF2BP2) is involved in insulin resistance in HepG2 cells after arsenic exposure through the peroxisome-proliferator-activated receptor γ (PPAR-γ) / glucose transporter 4 (GLUT4) pathway. Methods Cell viability was determined using cell counting kit 8 (CCK8) and an appropriate NaAsO2 infection dose was determined. A cellular arsenic exposure model of HepG2 cells was established by four concentrations of NaAsO2 solution for 24 h (the experiment was divided into four groups: 0, 2, 4, and 8 μmol·L−1); HepG2 cells were firstly treated with pcDNA3.1-IGF2BP2 and pcDNA3.1-NC respectively for 6 h, then with 8 μmol·L−1 NaAsO2 for 24 h to establish a IGF2BP2 overexpression cell model (the experiment was divided into 4 groups: control, NaAsO2, NaAsO2+pcDNA3.1-IGF2BP2, and NaAsO2+pcDNA3.1-NC); finally the cells were subject to 100 nmol·L−1 insulin stimulation for 30 min. Glycogen and glucose in HepG2 cells were determined by glycogen and glucose assay kits; mRNA expression levels of IGF2BP2 were measured by quantitative real-time PCR; protein expression levels of IGF2BP2, PPAR-γ, and GLUT4 in HepG2 were detected by Western blot (WB); and the binding of IGF2BP2 to PPAR-γ and PPAR-γ to GLUT4 was verified by co-immunoprecipitation (CO-IP) experiment. Results The results of CCK8 experiment showed a dose-effect relationship between NaAsO2 concentration and cell viability. When the concentration of NaAsO2 was ≥4 μmol·L−1 , the cell viabilities were lower than that of the control group (P <0.05). With the increasing dose of NaAsO2 infection, reduced glucose consumption and glycogen levels in HepG2 cells were found in the 2, 4, and 8 μmol·L−1 NaAsO2 treatment groups compared to the control group (P <0.05). The difference between the mRNA expression level of IGF2BP2 in the HepG2 cells treated with 4 or 8 μmol L−1 NaAsO2 and the control group was significant (P <0.05). In the IGF2BP2 overexpression cell model, compared with the control group, glucose consumption and glycogen levels were lowered in the NaAsO2 group (P <0.05), the mRNA expression level of IGF2BP2 and the protein expression levels of IGF2BP2, PPAR-γ, and GLUT4 in the cell membrane were all decreased (P <0.05). Compared with the NaAsO2 group, the glucose consumption and glycogen levels were increased in the NaAsO2+pcDNA3.1-IGF2BP2 group (P <0.05), and the mRNA expression level of IGF2BP2 and the protein expression levels of IGF2BP2, PPAR-γ, and GLUT4 in the cell membrane were all increased (P <0.05). The results of CO-IP experiments showed that IGF2BP2 interacted with PPAR-γ as well as PPAR-γ with GLUT4 protein. Conclusion IGF2BP2 is involved in arsenic exposure-induced insulin resistance in HepG2 cells by acting on the PPAR-γ/GLUT4 pathway.
3.Research on the construction and application of an intelligent internet of things-enabled dental chair platform based on dental chair domain interconnection
Xinyao QIAN ; Luwei LIU ; Yunwei SONG ; Yuxi WANG ; Kejia ZHANG ; Ning DAI ; Chenggang LI ; Bin WU ; Lizhe XIE ; Zhida SUN ; Lin WANG ; Bin YAN
Chinese Journal of Stomatology 2025;60(11):1274-1280
To address the problem of data silos in dental specialties caused by equipment heterogeneity, this study developed an Intelligent Internet of Things (IoT)-enabled dental chair platform (hereinafter referred to as the intelligent platform) based on the concept of medical-engineering integration. The platform adopts a three-tier chair-domain interconnection architecture: the bottom tier integrates multi-source sensors and standardized interfaces for automated data acquisition and linkage with hospital information systems; the middle tier provides clinic-level management and remote teaching collaboration; and the top tier employs a blockchain-based secure cloud database for resource allocation and data management. Clinical validation at The Affiliated Stomatological Hospital of Nanjing Medical University demonstrated that, compared with a control group from the same period in 2023, the trial group achieved a 38.0% increase in average daily patient visits (80.6±6.8 vs. 58.4±5.2, t=15.16, P<0.001), a 24.6% reduction in average treatment time [(36.1±6.3) min vs. (47.9±8.5) min, t=7.72, P<0.001], a 39.2% reduction in waiting time [23.3 (16.5, 30.1) min vs. 38.3 (28.3, 48.3) min, U=32.00, P<0.001], a 30.4% reduction in equipment idle rate [8.7% (5.1%, 12.3%) vs. 12.5% (7.4%, 17.6%), U=251.00, P=0.003], and an increase in patient satisfaction from 88.2% (1 519/1 723) to 94.3% (2 186/2 318) ( t=7.26, P<0.001). User research confirmed that the functions most favored by clinicians and patients were "dental chair parameter updating and clinical data integration" [74.7% (80/107)] and "chairside display of diagnostic images" [76.8% (119/155)], respectively. Looking forward, the intelligent platform has the potential to integrate artificial intelligence-assisted diagnosis and 5G-enabled multicenter collaboration to further expand its clinical applications and accelerate the digital transformation of dental healthcare.
4.Analysis of the efficacy and influencing factors of immunotherapy in gastric cancer liver metastasic patients
Tingting LU ; Yunhe GAO ; Gan ZHANG ; Haiya ZHANG ; Yi LIU ; Zhida CHEN ; Hongqing XI
Chinese Journal of Surgery 2025;63(2):136-146
Objective:To explore the efficacy and factors affecting the treatment of gastric cancer liver metastasis (GCLM) with immune checkpoint inhibitors (ICI).Methods:This is a retrospective cohort study. Clinical and pathological data of 588 patients with GCLM treated at the Department of General Surgery, First Medical Center, People′s Liberation Army General Hospital, from January 2018 to December 2022 were retrospectively collected. There were 491 males and 97 females, aged ( M(IQR)) 60(14) years (range: 18 to 86 years). Patients were divided into an ICI treatment group ( n=142) and a non-ICI treatment group ( n=446) based on whether they received ICI therapy. Clinical and pathological data between the two groups were compared using the χ2 test or Mann-Whitney U test. Propensity score matching (PSM) was performed with cT stage, cN stage, surgical treatment, targeted therapy, and biomarkers as covariates, using a 1∶1 nearest neighbor matching method with a caliper value of 0.2. Univariate and multivariate analyses were conducted using Cox proportional hazards regression models, with relevant variables selected through forward stepwise regression. Survival curves were plotted using the Kaplan-Meier method, and group differences were compared using the Log-rank test. Subgroup analysis was conducted to identify potential beneficiary populations for ICI through forest plots. Results:After PSM, 114 patients were included in each group, and there were no statistically significant differences in the baseline data between the two groups (all P>0.05). The results of Cox multivariate analysis after PSM showed that cN2-3 stage ( HR=1.348, 95% CI: 1.091 to 1.665, P=0.006) and peritoneal metastasis ( HR=1.877, 95% CI:1.360 to 2.590, P<0.01) were independent risk factors for survival in GCLM patients; radical surgery ( HR=0.391, 95% CI: 0.305 to 0.501, P<0.01), immunotherapy ( HR=0.630, 95% CI: 0.503 to 0.788, P<0.01), and deficient DNA mismatch repair (dMMR) or combined positive score (CPS)≥5 ( HR=0.454, 95% CI: 0.320 to 0.644, P<0.01) were independent protective factors for survival in GCLM patients. After PSM, the overall survival was 12.4 (13.0) months in the non-immunotherapy group and 17.6 (17.8) months in the immunotherapy group (Log-rank test: P=0.029). Subgroup analysis showed that female patients, those with primary tumors located in the upper stomach, cN2-3 stage, one liver metastasis, synchronous liver metastasis, receiving targeted therapy, and those with dMMR or CPS≥5 were more likely to benefit from ICI therapy (all P<0.05). Conclusions:ICI prolongs overall survival in GCLM patients. Female patients, those with primary tumors located in the upper stomach, cN2-3 stage, one liver metastasis, synchronous liver metastasis, receiving targeted therapy, and those with dMMR or CPS≥5 are more likely to benefit from ICI therapy.
5.Analysis of the therapeutic effects of traditional laparoscopic surgery,natural orifice specimen extraction surgery,and intersphincteric resection surgery in the treatment of low rectal cancer
Wenxi LI ; Xin ZHENG ; Baoxin SUN ; Haisheng ZHANG ; Zhida ZHU ; Enhong ZHAO
Journal of Clinical Surgery 2025;33(6):632-636
Objective To investigate the effects of traditional laparoscopic surgery,natural orifice specimen extraction surgery(NOSES),and intersphincteric resection(ISR)on treatment outcomes and quality of life in patients with low rectal cancer.Methods A total of 152 patients with low rectal cancer who were admitted from January 2020 to June 2022,and they were divided into the traditional laparoscopic group(49 cases),the NOSES group(51 cases),and the ISR group(52 cases)according to the surgical method.The operation status,postoperative recovery status,pain,anal function recovery status,quality of life and complications were compared in the 3 groups.Results The operation time of the traditional laparoscopic group[(193.98±12.31)min]was lower than that of the NOSES group[(203.54±15.02)min]and the ISR group[(199.85±11.98)min](P<0.05),operation time of NOSES group and ISR group was no difference(P>0.05).The first exhaust time[(60.21±10.05)h],the first time of getting out of bed[(37.52±6.21)h],and the length of postoperative hospital stay[(12.51±1.47)d]in the traditional laparoscopic group were all higher than those in the NOSES group[(51.06±8.67)h,(30.13±4.92)h,and(11.27±)1.23)d]and ISR group[(53.19±9.24)h,(28.97±4.71)h,(11.73±1.35)d](P<0.05),and there were no statistically significant differences in the first exhaust time,the first time to get out of bed,and the length of postoperative hospital stay between the NOSES and ISR groups(P>0.05).There was no statistically significant difference in the Visual Analogue Scale(VAS)scores for pain at 4 hours,24 hours,and 48 hours after surgery among the three groups(P>0.05).The VAS scores of the three groups at 24 hours after surgery were higher than those at 4 hours and 48 hours after surgery,and the difference was statistically significant(P<0.05).The VAS scores of the three groups at 48 hours after surgery were higher than those at 4 hours after surgery,and the difference was statistically significant(P<0.05).The NOSES group's Wexner score[(4.93±0.76)points]at 3 months after surgery and Wexner score[(3.21±0.42)points]at 6 months after surgery were lower than those of the ISR group[(6.32±0.93)points,(4.48±0.54)points]and the traditional laparoscopic group[(5.93±0.81)points,(4.01±0.53)points](P<0.05),and the Wexner score of the 3 groups at 3 months after surgery was lower than that at 1 month after surgery(P<0.05).The EORTC QLQ-C30 score of the NOSES group at 3 months after surgery was(74.82±4.01)points,and that at 6 months was(85.49±4.93)points,which were higher than those of the ISR group[(67.05±5.03)points and(71.64±4.21)points]and the traditional laparoscopic group[(70.42±3.92)points,(76.28±4.48)points](P<0.05),and the EORTC QLQ-C30 scores of the traditional laparoscopic group at 3 and 6 months after surgery were higher than those of the ISR group,and the difference was statistically significant(P<0.05).The EORTC QLQ-C30 score of the 3 groups at 6 months after surgery was higher than that before surgery and 3 months after surgery(P<0.05),and the EORTC QLQ-C30 score of the 3 groups at 3 months after surgery was higher than that before surgery(P<0.05).There was no significant difference in the incidence of total complications among the three groups(P>0.05).Conclusion Compared with traditional laparoscopic surgery for low rectal cancer,the NOSES and ISR methods accelerate postoperative bowel function recovery,and the NOSES methods have advantages in anal function recovery and better and satisfactory quality of life.
6.Chrm3 regulates LPS-induced inflammation in peritoneal macrophages in Lbp-/-mice via the MAPK/ERK signaling pathway
Zhida CHEN ; Bin FU ; Sidi LI ; Sai LIU ; Zhongkun GUO ; Yue ZHANG ; Kezhou WANG
Chinese Journal of Comparative Medicine 2025;35(4):69-78
Objective To investigate the role of cholinergic receptor muscarinic 3(Chrm3)in regulating lipopolysaccharide(LPS)-induced inflammation in peritoneal macrophages in lipopolysaccharide binding protein(LBP)-knockout(Lbp-/-)mice.Methods Peritoneal macrophages were isolated from wild-type and Lbp-/-mice to establish an LPS-induced inflammation model.Chrm3 expression in Lbp-/-mouse peritoneal macrophages was inhibited by 1,1-dimethyl-4-diphenylacetoxypiperidinium iodide(4-damp)and small interfering(siRNA)and Chrm3 overexpression was achieved by lentivirus transfection.For 4-damp inhibition,cells were divided into control,LPS,and inhibitor groups,and for siRNA transfection,cells were divided into control,LPS,si-normal control group,and si-Chrm3 groups.For overexpression,cells were divided into control,LPS,negative control,and overexpression groups.Changes in Chrm3 in response to LPS stimulation were verified by Western blot.The effects of 4-damp,si-Chrm3,and lentivirus on cell inflammation and survival were confirmed by Cell Counting Kit-8,quantitative polymerase chain reaction,and Western blot assays.Results Chrm3 protein expression was significantly elevated in Lbp-/-peritoneal macrophages post-LPS stimulation(P<0.001),whereas there was no notable change in wild-type cells.The cell survival rate was significantly increased in the 4-damp and si-Chrm3 groups(P<0.05,P<0.01),and cell survival was significantly reduced in the overexpression group(P<0.01).Furthermore,4-damp and si-Chrm3 significantly reduced expression levels of the inflammatory factors tumor necrosis factor(TNF)-α,interleukin(IL)-1β,IL-6(P<0.01,P<0.001),and phospho-extracellular signal-regulated kinase(p-ERK)(P<0.01,P<0.001),which are associated with cell damage and inflammation.In contrast,TNF-α,IL-1β,IL-6(P<0.001),and p-ERK protein(P<0.001)were significantly elevated in the overexpression group.Conclusions LPS stimulation upregulated the expression of Chrm3 and proinflammatory cytokines in Lbp-/-peritoneal macrophages.Specific downregulation of Chrm3 by 4-damp and si-Chrm3 significantly decreased LPS-induced proinflammatory cytokines in Lbp-/-peritoneal macrophages,while upregulation of Chrm3 using overexpressing lentivirus significantly elevated the expression of related inflammatory factors.Chrm3 is implicated in the regulation of the LPS-induced inflammation response in peritoneal macrophages in Lbp-/-mice.
7.Research on the construction and application of an intelligent internet of things-enabled dental chair platform based on dental chair domain interconnection
Xinyao QIAN ; Luwei LIU ; Yunwei SONG ; Yuxi WANG ; Kejia ZHANG ; Ning DAI ; Chenggang LI ; Bin WU ; Lizhe XIE ; Zhida SUN ; Lin WANG ; Bin YAN
Chinese Journal of Stomatology 2025;60(11):1274-1280
To address the problem of data silos in dental specialties caused by equipment heterogeneity, this study developed an Intelligent Internet of Things (IoT)-enabled dental chair platform (hereinafter referred to as the intelligent platform) based on the concept of medical-engineering integration. The platform adopts a three-tier chair-domain interconnection architecture: the bottom tier integrates multi-source sensors and standardized interfaces for automated data acquisition and linkage with hospital information systems; the middle tier provides clinic-level management and remote teaching collaboration; and the top tier employs a blockchain-based secure cloud database for resource allocation and data management. Clinical validation at The Affiliated Stomatological Hospital of Nanjing Medical University demonstrated that, compared with a control group from the same period in 2023, the trial group achieved a 38.0% increase in average daily patient visits (80.6±6.8 vs. 58.4±5.2, t=15.16, P<0.001), a 24.6% reduction in average treatment time [(36.1±6.3) min vs. (47.9±8.5) min, t=7.72, P<0.001], a 39.2% reduction in waiting time [23.3 (16.5, 30.1) min vs. 38.3 (28.3, 48.3) min, U=32.00, P<0.001], a 30.4% reduction in equipment idle rate [8.7% (5.1%, 12.3%) vs. 12.5% (7.4%, 17.6%), U=251.00, P=0.003], and an increase in patient satisfaction from 88.2% (1 519/1 723) to 94.3% (2 186/2 318) ( t=7.26, P<0.001). User research confirmed that the functions most favored by clinicians and patients were "dental chair parameter updating and clinical data integration" [74.7% (80/107)] and "chairside display of diagnostic images" [76.8% (119/155)], respectively. Looking forward, the intelligent platform has the potential to integrate artificial intelligence-assisted diagnosis and 5G-enabled multicenter collaboration to further expand its clinical applications and accelerate the digital transformation of dental healthcare.
8.Chrm3 regulates LPS-induced inflammation in peritoneal macrophages in Lbp-/-mice via the MAPK/ERK signaling pathway
Zhida CHEN ; Bin FU ; Sidi LI ; Sai LIU ; Zhongkun GUO ; Yue ZHANG ; Kezhou WANG
Chinese Journal of Comparative Medicine 2025;35(4):69-78
Objective To investigate the role of cholinergic receptor muscarinic 3(Chrm3)in regulating lipopolysaccharide(LPS)-induced inflammation in peritoneal macrophages in lipopolysaccharide binding protein(LBP)-knockout(Lbp-/-)mice.Methods Peritoneal macrophages were isolated from wild-type and Lbp-/-mice to establish an LPS-induced inflammation model.Chrm3 expression in Lbp-/-mouse peritoneal macrophages was inhibited by 1,1-dimethyl-4-diphenylacetoxypiperidinium iodide(4-damp)and small interfering(siRNA)and Chrm3 overexpression was achieved by lentivirus transfection.For 4-damp inhibition,cells were divided into control,LPS,and inhibitor groups,and for siRNA transfection,cells were divided into control,LPS,si-normal control group,and si-Chrm3 groups.For overexpression,cells were divided into control,LPS,negative control,and overexpression groups.Changes in Chrm3 in response to LPS stimulation were verified by Western blot.The effects of 4-damp,si-Chrm3,and lentivirus on cell inflammation and survival were confirmed by Cell Counting Kit-8,quantitative polymerase chain reaction,and Western blot assays.Results Chrm3 protein expression was significantly elevated in Lbp-/-peritoneal macrophages post-LPS stimulation(P<0.001),whereas there was no notable change in wild-type cells.The cell survival rate was significantly increased in the 4-damp and si-Chrm3 groups(P<0.05,P<0.01),and cell survival was significantly reduced in the overexpression group(P<0.01).Furthermore,4-damp and si-Chrm3 significantly reduced expression levels of the inflammatory factors tumor necrosis factor(TNF)-α,interleukin(IL)-1β,IL-6(P<0.01,P<0.001),and phospho-extracellular signal-regulated kinase(p-ERK)(P<0.01,P<0.001),which are associated with cell damage and inflammation.In contrast,TNF-α,IL-1β,IL-6(P<0.001),and p-ERK protein(P<0.001)were significantly elevated in the overexpression group.Conclusions LPS stimulation upregulated the expression of Chrm3 and proinflammatory cytokines in Lbp-/-peritoneal macrophages.Specific downregulation of Chrm3 by 4-damp and si-Chrm3 significantly decreased LPS-induced proinflammatory cytokines in Lbp-/-peritoneal macrophages,while upregulation of Chrm3 using overexpressing lentivirus significantly elevated the expression of related inflammatory factors.Chrm3 is implicated in the regulation of the LPS-induced inflammation response in peritoneal macrophages in Lbp-/-mice.
9.Analysis of the therapeutic effects of traditional laparoscopic surgery,natural orifice specimen extraction surgery,and intersphincteric resection surgery in the treatment of low rectal cancer
Wenxi LI ; Xin ZHENG ; Baoxin SUN ; Haisheng ZHANG ; Zhida ZHU ; Enhong ZHAO
Journal of Clinical Surgery 2025;33(6):632-636
Objective To investigate the effects of traditional laparoscopic surgery,natural orifice specimen extraction surgery(NOSES),and intersphincteric resection(ISR)on treatment outcomes and quality of life in patients with low rectal cancer.Methods A total of 152 patients with low rectal cancer who were admitted from January 2020 to June 2022,and they were divided into the traditional laparoscopic group(49 cases),the NOSES group(51 cases),and the ISR group(52 cases)according to the surgical method.The operation status,postoperative recovery status,pain,anal function recovery status,quality of life and complications were compared in the 3 groups.Results The operation time of the traditional laparoscopic group[(193.98±12.31)min]was lower than that of the NOSES group[(203.54±15.02)min]and the ISR group[(199.85±11.98)min](P<0.05),operation time of NOSES group and ISR group was no difference(P>0.05).The first exhaust time[(60.21±10.05)h],the first time of getting out of bed[(37.52±6.21)h],and the length of postoperative hospital stay[(12.51±1.47)d]in the traditional laparoscopic group were all higher than those in the NOSES group[(51.06±8.67)h,(30.13±4.92)h,and(11.27±)1.23)d]and ISR group[(53.19±9.24)h,(28.97±4.71)h,(11.73±1.35)d](P<0.05),and there were no statistically significant differences in the first exhaust time,the first time to get out of bed,and the length of postoperative hospital stay between the NOSES and ISR groups(P>0.05).There was no statistically significant difference in the Visual Analogue Scale(VAS)scores for pain at 4 hours,24 hours,and 48 hours after surgery among the three groups(P>0.05).The VAS scores of the three groups at 24 hours after surgery were higher than those at 4 hours and 48 hours after surgery,and the difference was statistically significant(P<0.05).The VAS scores of the three groups at 48 hours after surgery were higher than those at 4 hours after surgery,and the difference was statistically significant(P<0.05).The NOSES group's Wexner score[(4.93±0.76)points]at 3 months after surgery and Wexner score[(3.21±0.42)points]at 6 months after surgery were lower than those of the ISR group[(6.32±0.93)points,(4.48±0.54)points]and the traditional laparoscopic group[(5.93±0.81)points,(4.01±0.53)points](P<0.05),and the Wexner score of the 3 groups at 3 months after surgery was lower than that at 1 month after surgery(P<0.05).The EORTC QLQ-C30 score of the NOSES group at 3 months after surgery was(74.82±4.01)points,and that at 6 months was(85.49±4.93)points,which were higher than those of the ISR group[(67.05±5.03)points and(71.64±4.21)points]and the traditional laparoscopic group[(70.42±3.92)points,(76.28±4.48)points](P<0.05),and the EORTC QLQ-C30 scores of the traditional laparoscopic group at 3 and 6 months after surgery were higher than those of the ISR group,and the difference was statistically significant(P<0.05).The EORTC QLQ-C30 score of the 3 groups at 6 months after surgery was higher than that before surgery and 3 months after surgery(P<0.05),and the EORTC QLQ-C30 score of the 3 groups at 3 months after surgery was higher than that before surgery(P<0.05).There was no significant difference in the incidence of total complications among the three groups(P>0.05).Conclusion Compared with traditional laparoscopic surgery for low rectal cancer,the NOSES and ISR methods accelerate postoperative bowel function recovery,and the NOSES methods have advantages in anal function recovery and better and satisfactory quality of life.
10.Analysis of the efficacy and influencing factors of immunotherapy in gastric cancer liver metastasic patients
Tingting LU ; Yunhe GAO ; Gan ZHANG ; Haiya ZHANG ; Yi LIU ; Zhida CHEN ; Hongqing XI
Chinese Journal of Surgery 2025;63(2):136-146
Objective:To explore the efficacy and factors affecting the treatment of gastric cancer liver metastasis (GCLM) with immune checkpoint inhibitors (ICI).Methods:This is a retrospective cohort study. Clinical and pathological data of 588 patients with GCLM treated at the Department of General Surgery, First Medical Center, People′s Liberation Army General Hospital, from January 2018 to December 2022 were retrospectively collected. There were 491 males and 97 females, aged ( M(IQR)) 60(14) years (range: 18 to 86 years). Patients were divided into an ICI treatment group ( n=142) and a non-ICI treatment group ( n=446) based on whether they received ICI therapy. Clinical and pathological data between the two groups were compared using the χ2 test or Mann-Whitney U test. Propensity score matching (PSM) was performed with cT stage, cN stage, surgical treatment, targeted therapy, and biomarkers as covariates, using a 1∶1 nearest neighbor matching method with a caliper value of 0.2. Univariate and multivariate analyses were conducted using Cox proportional hazards regression models, with relevant variables selected through forward stepwise regression. Survival curves were plotted using the Kaplan-Meier method, and group differences were compared using the Log-rank test. Subgroup analysis was conducted to identify potential beneficiary populations for ICI through forest plots. Results:After PSM, 114 patients were included in each group, and there were no statistically significant differences in the baseline data between the two groups (all P>0.05). The results of Cox multivariate analysis after PSM showed that cN2-3 stage ( HR=1.348, 95% CI: 1.091 to 1.665, P=0.006) and peritoneal metastasis ( HR=1.877, 95% CI:1.360 to 2.590, P<0.01) were independent risk factors for survival in GCLM patients; radical surgery ( HR=0.391, 95% CI: 0.305 to 0.501, P<0.01), immunotherapy ( HR=0.630, 95% CI: 0.503 to 0.788, P<0.01), and deficient DNA mismatch repair (dMMR) or combined positive score (CPS)≥5 ( HR=0.454, 95% CI: 0.320 to 0.644, P<0.01) were independent protective factors for survival in GCLM patients. After PSM, the overall survival was 12.4 (13.0) months in the non-immunotherapy group and 17.6 (17.8) months in the immunotherapy group (Log-rank test: P=0.029). Subgroup analysis showed that female patients, those with primary tumors located in the upper stomach, cN2-3 stage, one liver metastasis, synchronous liver metastasis, receiving targeted therapy, and those with dMMR or CPS≥5 were more likely to benefit from ICI therapy (all P<0.05). Conclusions:ICI prolongs overall survival in GCLM patients. Female patients, those with primary tumors located in the upper stomach, cN2-3 stage, one liver metastasis, synchronous liver metastasis, receiving targeted therapy, and those with dMMR or CPS≥5 are more likely to benefit from ICI therapy.

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